Hyperproliferation and oxidative stress induced by hyperglycemia in mesangial cells plays crucial roles in the pathological process of diabetic nephropathy. Farrerol, isolated from rhododendron leaves, possesses broad anti-oxidative and anti-inflammatory properties towards several diseases, but its role in diabetic neuropathy remains unclear. The aim of this study was to evaluate the effects of farrerol in high glucose induced mesangial cell injury, and to explore underlying molecular mechanisms. Our results showed that high glucose in vitro conditions significantly stimulated cell proliferation, inflammatory cytokine secretion, extracellular matrix deposition, excessive oxidative stress, and NADPH oxidase activity in mesangial cells. Levels of NADPH oxidase 4 (Nox4) expression, ERK1/2 phosphorylation, and TGF-β1/Smad2 activation were significantly induced by high glucose conditions in mesangial cells. Inversely, farrerol treatments at 40, 60, and 80 μM concentrations, dose-dependently alleviated this molecular damage by high glucose in mesangial cells. We also found that restoration of Nox4 expression abolished the protective effects of farrerol on high glucose-induced proliferation and reactive oxygen species generation. Furthermore, pretreatment with the Nox4 inhibitor diphenyliodonium or the ERK1/2 pathway inhibitor PD98059, displayed similar ameliorated effects of farrerol on high glucose-induced mesangial cell damage. Taken together, these data suggest that farrerol displays protective effects on high glucose induced mesangial cell injury, partly through the Nox4-mediated ROS/ERK1/2 signaling pathway. These observations may provide novel insights into the application of farrerol as a diabetic neuropathy treatment.

中文翻译：

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Farrerol通过ROS / Nox4 / ERK1 / 2途径减轻高糖诱导的肾系膜细胞损伤。

高血糖在肾小球系膜细胞中引起的过度增殖和氧化应激在糖尿病性肾病的病理过程中起着至关重要的作用。从杜鹃叶子中分离出的Farrerol对多种疾病具有广泛的抗氧化和抗炎特性，但在糖尿病性神经病中的作用尚不清楚。这项研究的目的是评估法雷洛尔在高糖诱导的系膜细胞损伤中的作用，并探讨潜在的分子机制。我们的结果表明，高葡萄糖体外条件明显刺激了系膜细胞的细胞增殖，炎症性细胞因子分泌，细胞外基质沉积，过度的氧化应激和NADPH氧化酶活性。NADPH氧化酶4（Nox4）表达水平，ERK1 / 2磷酸化，高糖条件下肾小球系膜细胞明显诱导了TGF-β和TGF-β1/ Smad2的活化。相反，在40、60和80μM浓​​度下的farrerol处理剂量依赖性地减轻了系膜细胞中高葡萄糖引起的这种分子损伤。我们还发现，Nox4表达的恢复取消了法瑞罗对高葡萄糖诱导的增殖和活性氧生成的保护作用。此外，用Nox4抑制剂二苯基碘鎓或ERK1 / 2途径抑制剂PD98059进行的预处理显示了法瑞罗对高糖诱导的系膜细胞损伤的类似改善作用。综上所述，这些数据表明，法雷洛尔部分通过Nox4介导的ROS / ERK1 / 2信号通路对高糖诱导的系膜细胞损伤显示出保护作用。